Mottled (Mo) mice are animal models for an X-linked recessive copper deficiency disorder in humans known as
Menkes disease. This disorder in human and mouse is the result of mutation(s) in the P-type ATPase Atp7a, which
involved in copper transport. There are at least nine Mo mouse mutants each having varying degrees of phenotypic effect,
from death at the end of gestation to lack of coat pigment. Pewter (Atp7aMo-pew) mice have the mildest phenotypic effect
with only coat color being affected. We have identified a mutation in the Atp7a locus of mottled pewter at the genomic
level. Genomic DNA of seven independent Mo allelic mice (Atp7aMo-to, Atp7aMo-br, Atp7aMo-vbr, Atp7aMo-dp,
Atp7aMo-pew, Atp7aMo-blo and Atp7aMo-unk ) were studied by RFLP analysis using several exon probes derived from
a murine Atp7a cDNA. We identified an EcoR1 polymorphism at the Atp7a locus in Atp7aMo-pew with a probe specific
for exons 20 and 21 of Atp7a. This RFLP was co-inherited in three generation pedigrees only in Atp7aMo-pew. DNA
sequence analysis of subclones revealed a 197 bp deletion in intron 20 of Atp7aMo-pew when compared with control wild-type. Sequence analysis of intron 20 revealed the deleted sequence to be a repeat element (type of repeat to be determined).
Whether this intronic deletion is involved in manifesting this minor phenotype has yet to be determined. PCR of this STS
provides a quick method to identify the Atp7aMo-pew allele.